Gangliosides located at the outer leaflet of plasma membrane are molecules that either participate in recognizing of exogenous ligand molecules or exhibit their own receptor activity, which are both essential phenomena for cell communication and signaling as well as for virus and toxin entry. Regulatory mechanisms of lipid-mediated recognition are primarily subjected to the physical status of the membrane in close vicinity of the receptor. Concerning the multivalent receptor activity of the ganglioside GM1, several regulatory strategies dealing with GM1 clustering and cholesterol involvement have been proposed. So far however, merely the isolated issues were addressed and no interplay between them investigated. In this work, several advanced fluorescence techniques such as Z-scan fluorescence correlation spectroscopy, Förster resonance energy transfer combined with Monte Carlo simulations, and a newly developed fluorescence antibunching assay were employed to give a more complex portrait of clustering and cholesterol involvement in multivalent ligand recognition of GM1. Our results indicate that membrane properties have an impact on a fraction of GM1 molecules that is not available for the ligand binding. While at low GM1 densities (~1 %) it is the cholesterol that turns GM1 headgroups invisible, at higher GM1 level (~4 %) it is purely the local density of GM1 molecules that inhibits the recognition. At medium GM1 content, cooperation of the two phenomena occurs. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.

Department of Biophysical Chemistry J Heyrovsky Institute of Physical Chemistry of the Academy of Sciences of the Czech Republic Dolejškova 2155 3 Prague 8 Cz 182 23 Czech Republic

Department of Biophysical Chemistry J Heyrovsky Institute of Physical Chemistry of the Academy of Sciences of the Czech Republic Dolejškova 2155 3 Prague 8 Cz 182 23 Czech Republic; Faculty of Science Charles University Prague Albertov 6 128 43 Prague 2 Czech Republic

Shemyakin Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science Ul Miklukho Maklaya 16 10 117997 Moscow GSP 7 Russian Federation

Citace poskytuje Crossref.org

Which Moiety Drives Gangliosides to Form Nanodomains?

Interleaflet organization of membrane nanodomains: What can(not) be resolved by FRET?

The impact of the glycan headgroup on the nanoscopic segregation of gangliosides

Interleaflet Coupling of Lipid Nanodomains - Insights From in vitro Systems

Membrane Protein Dimerization in Cell-Derived Lipid Membranes Measured by FRET with MC Simulations

Impact of GM1 on Membrane-Mediated Aggregation/Oligomerization of β-Amyloid: Unifying View

Lipid Driven Nanodomains in Giant Lipid Vesicles are Fluid and Disordered

GM1 Ganglioside Inhibits β-Amyloid Oligomerization Induced by Sphingomyelin

Time-resolved fluorescence in lipid bilayers: selected applications and advantages over steady state